The proposed Alzheimer Disease Research Center (ADRC) is a multidisciplinary effort that builds upon the experience gained in the University of Pittsburgh's NIA-funded Alzheimer's Program Project (AG03705). This proposal will expand the clinical and research support services already in place and will apply the latest methodological and technological advances to investigations of the pathophysiology of Alzheimer's Disease (AD). This approach will ensure excellent patient care and stimulate productive research both into causative molecular mechanisms of AD and into development of sensitive and reliable clinical diagnostic techniques. Only by understanding the molecular basis of AD and by acquiring the capacity for diagnosis early in the course of the disease will we be in a position to develop successful therapeutic approaches. The Research component of the ADRC will include both clinical and basic science studies. Clinical research will include neuroimaging studies using CT scanning and NMR imaging; neurophysiological evaluations using EEG spectral analysis; neurochemical analysis by means of CSF cholinesterase assays; in vivo 31P NMR spectroscopy and fluorescence spectroscopy; and neurophysiological assessments of communication and attention deficits. Postmortem and animal research studies will include evaluation of brain autopsy specimens using quantitative neuropathological and histological measures; high-field, high-resolution 13C and 31P NMR spectroscopy; brain cholinesterase assays; and membrane molecular dynamics.